OBJECTIVES: We are examining environmental and endogenous factors that contribute to the development of intestinal cancer. This involves determinations of etiological agents by a standard protocol and the levels of susceptibilities manifested by several strains of laboratory rats in response to such treatments. Those which manifest resistance will be further examined for nature of resistance as a biochemical rather than a classical immunological phenomenon. A model tumor system has been developed in which 100% of germfree and conventional Lobund strain Sprague-Dawley rats respond within 20 weeks to a standard protocol of 1,2 dimethylhydrazine with multiple intestinal carcinomas which can be counted. No rat has developed such tumors spontaneously. This experimental protocol will be used to assay a number of prophylactic and therapeutic procedures which relate to the disease problem in man. These will include cytototoxic and immunopotentiating drugs, radiation and radiation-induced bone marrow chimerism; and a new antitumor lipoprotein recovered from serums of pregnant rats. Agents which promote tumor growth will be examined in relation to metastasis. The principal goal of this program is the development of an experimental system for test and analysis which more closely relates to the disease in man, rather than the present system of transplanted tumors. The tumor model system has been tested in 190 Sprague-Dawley rats: all of them developed intestinal carcinomas within 20 weeks after administration of 1,2 dimethylhydrazine protocol described herein.